Potassium Fluoride → Ethyl 2-fluoro-4-[6-(1-trityl-1H-pyrazol-4-yl)-quinazolin-4-yl]benzoate

HRID 1792609노트

반응식

HRID 1792609 반응식
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[C:12]1[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:14]([F:23])[CH:13]=1.[C:24]([N:43]1[CH:47]=[C:46](B(O)O)[CH:45]=[N:44]1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[F-].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CN(C)C=O>[F:23][C:14]1[CH:13]=[C:12]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:46]4[CH:45]=[N:44][N:43]([C:24]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)[CH:47]=4)[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:22]=[CH:21][C:15]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17]

참가 물질

8

반응물 4

HCID 522689Potassium FluorideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 22031224Ethyl 4-(6-chloroquinazolin-4-yl)-2-fluorobenzoateHCID 22031737(1-Trityl-1H-pyrazol-4-yl)boronic acid

생성물 1

HCID 22031192Ethyl 2-fluoro-4-[6-(1-trityl-1H-pyrazol-4-yl)-quinazolin-4-yl]benzoate수율 70.1%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매2회HCID 6228Dimethylformamide용매

실험 절차

0.64 g ethyl 4-(6-chloroquinazolin-4-yl)-2-fluorobenzoate (compound in Production Example 385), 1.02 g 1-trityl-1H-4-pyrazolylboronic acid, 0.34 g potassium fluoride, 43 mg palladium (II) acetate, 0.11 g 2-(di-t-butylphosphino)biphenyl, 20 mL N,N-dimethylformamide and 2 mL water were heated at 70° C. for 24 hours under nitrogen atmosphere. Water was added thereto, the reaction solution was filtered, and crystals collected by filtration were washed with water. The crystals were dissolved in dichloromethane, washed with water and dried over sodium sulfate. The solvent was evaporated, and the residue was purified by NH silica gel column chromatography (hexane/ethyl acetate), to give 0.82 g of the title compound (pale yellow crystals).

후처리

  1. filtrationthe reaction solution was filtered
  2. filtrationcrystals collected by filtration
  3. washwere washed with water
  4. dissolutionThe crystals were dissolved in dichloromethane
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was evaporated
  8. customthe residue was purified by NH silica gel column chromatography (hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-a7c568d94a0f4e84ae663770a21c8249
출처 데이터셋
uspto-grants-2006_07
특허 번호
US07074801B1

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